A systematic investigation of the selective alkylation of the phosphate oxygen of nucleic acids by certain cationic alkylating agents will be carried out. Non-alkylating analogues did not covalently modify the nucleic acids but provide means for measuring non-covalent binding. The modified NA containing up to stoichiometric binding (one mole of reagent residue per phosphate) will be characterized by physical and organic methods. The process of alkylation will be studied. Effects on selected mutant strains will be determined.